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. 2023 May 2;63(5):ezad115.
doi: 10.1093/ejcts/ezad115.

Valvular complex and tissue remodelling in ovine functional tricuspid regurgitation

Artur Iwasieczko  1   2 , Manikantam Gaddam  3 , Boguslaw Gaweda  1   2 , Austin Goodyke  3 , Mrudang Mathur  4 , Chien-Yu Lin  4 , Joseph Zagorski  3 , Monica Solarewicz  1 , Stephen Cohle  5 , Manuel Rausch  4 , Tomasz A Timek  1
Affiliations

Valvular complex and tissue remodelling in ovine functional tricuspid regurgitation

Artur Iwasieczko et al. Eur J Cardiothorac Surg. .

Abstract

Objectives: Pathophysiology of function tricuspid regurgitation (FTR) is incompletely understood. We set out to comprehensively evaluate geometric and tissue remodelling of the tricuspid valve complex in ovine FTR.

Methods: Twenty adult sheep underwent left thoracotomy and pulmonary artery banding (PAB) to induce right heart pressure overload and FTR. After 8 weeks, 17 surviving animals and 10 healthy controls (CTL) underwent sternotomy, echocardiography and implantation of sonomicrometry crystals on right ventricle and tricuspid valvular apparatus. Haemodynamic and sonomicrometry data were acquired in all animals after weaning from cardiopulmonary bypass. Leaflet tissue was harvested for pentachrome histologic analysis and biomechanical testing.

Results: Animal weight was 62 ± 5 and 63 ± 3 kg for CTL and PAB, respectively (P = 0.6). At terminal procedure, systolic pulmonary artery pressure was 22 ± 3 and 40 ± 7 mmHg for CTL and PAB, respectively (P = 0.0001). The mean TR grade (+0-4) was 0.8 ± 0.4 and 3.2 ± 1.2 (P = 0.0001) for control and banded animals, respectively. Right ventricle volume (126 ± 13 vs 172 ± 34 ml, P = 0.0019), tricuspid annular area (651 ± 109 vs 865 ± 247 mm2, P = 0.037) and area between papillary muscle tips (162 ± 51 vs 302 ± 75 mm2, P = 0.001) increased substantially while systolic excursion of anterior leaflet decreased significantly (23.8 ± 6.1° vs 7.4 ± 4.5°, P = 0.001) with banding. Total leaflet surface area increased from 806 ± 94 to 953 ± 148 mm2 (P = 0.009), and leaflets became thicker and stiffer.

Conclusions: Detailed analysis of the tricuspid valve complex revealed significant ventricular, annular, subvalvular and leaflet remodelling to be associated with ovine functional tricuspid regurgitation. Durable surgical repair of severe FTR may require a multi-level approach to the valvular apparatus.

Keywords: Functional tricuspid regurgitation; Tricuspid valve; Valve repair.

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Figures

Figure 1:
Figure 1:
Schematic representation of the right ventricle with implanted sonomicrometry crystals around the tricuspid annulus and on the right ventricular epicardium, papillary muscle tips and central edge of the anterior leaflet. APM: anterior papillary muscle; PPM: posterior papillary muscle; SPM: septal papillary muscle.
Figure 2:
Figure 2:
Intra-operative images of pulmonary artery banding animals. (A) Ovine heart after 8 weeks of pulmonary banding with remarkable right atrial and right ventricular enlargement. (B) Epicardial echocardiography demonstrating right ventricular and annular dilation as well as impressive right atrial dilation associated with pulmonary artery banding. (C) Colour Doppler confirming presence of severe functional tricuspid regurgitation. (D) Instrumented heart after weaning from cardiopulmonary bypass with implanted epicardial sonomicrometry crystals and right and left ventricular pressure transducers.
Figure 3:
Figure 3:
Group mean and standard deviation for right ventricular volume (top panel), tricuspid annular area (middle panel) and area between papillary muscle tips (bottom panel) throughout the cardiac cycle in control (CTL) and banded (pulmonary artery banding) animals. ED: end diastole; EIVC: end-isovolumic contraction; EIVR: end-isovolumic contraction; ES: end systole.
Figure 4:
Figure 4:
Group mean and standard deviation for right ventricular free wall areal strain at basal (top panel) and mid-ventricle (bottom panel) throughout the cardiac cycle in control (CTL) and banded (pulmonary artery banding) animals. ED: end diastole; EIVC: end-isovolumic contraction; EIVR: end-isovolumic contraction; ES: end systole.
Figure 5:
Figure 5:
Group mean and standard deviation of anterior leaflet angle throughout the cardiac cycle in control (CTL) and banded (pulmonary artery banding) animals. ED: end diastole; EIVC: end-isovolumic contraction; EIVR: end-isovolumic contraction; ES: end systole.
Figure 6:
Figure 6:
Pentachrome staining at 10× magnification of anterior tricuspid valve leaflet from control (top) and pulmonary artery banded (bottom) animal (A). Group mean and standard deviation for control (CTL) and pulmonary artery banding (pulmonary artery banding) animals of leaflet thickness (B), cellularity (C), elastin content (D), collagen content (E) and mucin content (F).
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